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Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy
David J Benjamin1, Robert Hsu2
1Hoag Family Cancer Institute, Newport Beach, CA, United States.
Abstract:
The treatment of metastatic urothelial carcinoma has dramatically changed over the past decade with the approval of several therapies from multiple drug classes including immune checkpoint inhibitors, targeted therapies, and antibody drug conjugates. Although next generation sequencing of urothelial carcinoma has revealed multiple recurring mutations, only one targeted therapy has been developed and approved to date. Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has been approved for treating patients with select FGFR2 and FGFR3 alterations and fusions since 2019. Since then, emerging data has demonstrated efficacy of combining erdafitinib with immunotherapy in treating FGFR-altered urothelial carcinoma. Ongoing trials are evaluating the use of erdafitinib in non-muscle invasive urothelial carcinoma as well as in combination with enfortumab vedotin in the metastatic setting, while other FGFR targeted agents such as infigratinib, AZD4547, rogaratinib and pemigatinib continue to be in development. Future challenges will include strategies to overcome FGFR acquired resistance and efficacy and safety of combination therapies with erdafitinib and other FGFR targeted agents.
Insights
Fibroblast growth factor receptor (FGFR) inhibitors like erdafitinib offer new treatments for urothelial carcinoma. Research is exploring combinations with immunotherapy and other agents to improve outcomes and overcome resistance.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Metastatic urothelial carcinoma treatment has advanced with new drug classes.
- Targeted therapies, including FGFR inhibitors, are emerging.
- Erdafitinib is approved for specific FGFR alterations in urothelial carcinoma.
Purpose of the Study:
- To review the current landscape of FGFR-targeted therapies in urothelial carcinoma.
- To discuss the efficacy of combining erdafitinib with immunotherapy.
- To highlight ongoing research and future challenges in FGFR-targeted treatment.
Main Methods:
- Review of recent clinical trial data and emerging research.
- Analysis of approved and investigational FGFR inhibitors.
- Exploration of combination therapy strategies.
Main Results:
- Erdafitinib shows efficacy in FGFR-altered urothelial carcinoma.
- Combination of erdafitinib with immunotherapy demonstrates promise.
- Several FGFR inhibitors are in various stages of development.
Conclusions:
- FGFR inhibitors represent a significant advancement in urothelial carcinoma treatment.
- Combination therapies and overcoming resistance are key areas for future research.
- Ongoing trials are expanding the application of FGFR inhibitors.
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